Upload
chloe-allen
View
215
Download
0
Embed Size (px)
Citation preview
Treatment demand and drug related deaths:
results and hints from the VEdeTTE study
Patrizia SchifanoEMCDDA - 2006 Annual expert
meeting
Lisbon
ObjectivesObjectivesObjectivesObjectives
the effectviness of treatments
offered in public treatment centers
in preventing overdose mortality
among heroin users in Italy
The VEdeTTE Study has been designed to evaluate
ObjectivesObjectivesObjectivesObjectives
to describe treatment offer
tipologylenghttherapeutic aim
and differences among services
and….
to evaluate retantion in treatment according to type of treatment
and….
Design:Design:Design:Design:
National Multicenter Longitudinal Prospective Study:
Target population: heroin users seeking for treatment, >18 yrs old
115 (out of 554) PTCs (NHS)
Enrollment and follow-up: October 1998 - March 2000
Vital status ascertainment: March 2001
Study population: 10454 subjects
The cohortThe cohortThe cohortThe cohort
86% males 12% new clients Average age: 31 yrs 80% intravenous users 41% had previous overdose episodes 8.2% HIV positive (33.6 MV)
The TreatmentsThe TreatmentsThe TreatmentsThe Treatments
Pharmacological therapies
residential communitysemi-residential communityemergency center
Therapeutic community
psychoterapysupportcounsellingorientation and work fellowship
Psychosocial therapies
methadone detoxification
naltrexonedetoxification with syntomaticnot-substitutive syntomatic
methadone maintenance
The TreatmentsThe TreatmentsThe TreatmentsThe Treatments
Total time in treatment: 10,208 p-yrs (78%)
Total time out of treatment: 2,914 p-yrs (22%)
Median lenght of follow-up: 547 days (99%)
Average number of treatments per person: 3.1
The TreatmentsThe TreatmentsThe TreatmentsThe Treatments
Methadone Maintenance
Detoxification Methadone
Psychosocial Therapies
Other Pharmacological
Ntrt
Nsubjects
Average n per
person
Median
lenght (days)
Therapeutic Community 1830
11311
10684
5931
1876
1.2 192.5
2.3 28.0
1.7 120.06837
4764
1274
1563
3582 1.7
1.5
30.0
32.0
The sequence of treatments: starting with MMT …………….
The sequence of treatments: starting with MMT …………….
2nd treatment %
MMT 6,3
MD 74,7
TC 1,7
Other 12,2
No treatment 5,1
MMT 40,6
MD 12,9
TC 0,9
Other 25,8
No treatment 19,8
concluded(33.2%)
drop-out(20.4%)
MMT
N=4412
MD
N=1718
2nd treatment %
MMT 34,5
MD 34,6
TC 1,7
Other 26,6
No treatment 5,6
MMT 23,1
MD 47,0
TC 1,1
Other 21,5
No treatment 7,3
concluded(66.7%)
drop-out(20.4%)
The sequence of treatments: starting with MD.…………….
The sequence of treatments: starting with MD.…………….
Dose
Average: 40.9 mg/dayMedian: 39.7 mg/day
19% of subjects >60mg/day
Methadone Manteinance Methadone Manteinance
Mortality analysisMortality analysis
Study population: 10258
Observed deaths: 189
• 36.8% overdose
• 20.0% AIDS
• 15.8% violent causes
Males
Females
Rate /1000 p-y 95% CI
12.7
8.4
12.0
4.9 – 20.5
4.7 – 12.2
5.4 – 18.6
Mortality analysisMortality analysis
Total
in treatment
out of treatment
SMR 95% CI
3.9
22.8
9.9
5.7 – 7.8
8.6 – 11.4
Mortality analysisMortality analysis
total
16.7-27.4
Mortality and treatmentMortality and treatment
Study period: 18 months Deaths: 100 (53% of the total) Overdose deaths: 41 (59% of the total)
Mortality by overdose and treatment Mortality by overdose and treatment
Hazard Ratio of overdose mortality for heroin users in treatment, VEdeTTE study
Number of deaths
(41) Person-years Rate
1000 p-y Crude RR Adjusted RR* 95% IC
Out of treatment 31 2913.79 10.64 1.00 1.00 In treatment 10 10207.72 0.98 0.09 0.09 0.04 0.19
In treatment Methadone maintenance 7 5751.28 1.22 0.11 0.10 0.04 0.24 Therapeutic Community 0 1188.94 - - - - - Methadone detoxification 1 1495.72 0.67 0.06 0.07 0.01 0.50 Other pharmacological 1 422.59 2.37 0.22 0.37 0.05 2.76 Psychosocial 1 1349.23 0.74 0.07 0.07 0.01 0.55
* Adjusted for age, gender, psychiatric co-morbidity, HIV status, previous non fatal overdose, route of administration, length of use
Mortality by overdose and treatment Mortality by overdose and treatment
Hazard Ratio of overdose mortality for heroin users out of treatment by treatment andby time since last treatment , VEdeTTE study
Number of deaths (41) Person-years Rate 1000
p-y Crude
RR Adjusted
RR* 95% IC
In treatment 10 10207.72 0.98 1 - - Out treat ment 31 2913.79 10.64 10.86 11.11 5.29 23.35
Out of treatment Methadone maintenance 9 997.68 9.02 9.21 8.26 3.27 20.88
Therapeutic Community 5 231.74 21.58 22.02 23.00 7.63 69.31 Methadone detoxification 7 814.06 8.60 8.78 9.35 3.46 25.26 Other pharmacological 7 612.20 11.43 11.67 12.09 4.48 32.60 Psychosocial 3 250.46 11.98 12.23 22.31 5.88 84.58 Time since last treatment (days)
<=30 13 561.44 23.15 23.64 26.57 11.56 61.10 >30 18 2352.36 7.65 7.81 7.29 3.28 16.22
* Adjusted for age, gender, psychiatric co-morbidity, HIV status, previous non fatal overdose, route of administration, length of use
Is no treatment better than a short-period treatment?
Is no treatment better than a short-period treatment?
in treatment out of treatment
2.67 x 10002.67 x 1000 19.26 x 100019.26 x 1000
out of treatment out of treatment
7.7 x 10007.7 x 1000 7.7 x 10007.7 x 1000
1 month
A
B
Is no treatment better than a short-period treatment?
Is no treatment better than a short-period treatment?
Excess of mortality attributable to being in a short-term treatment in a 2-month period
5.52 deaths x 10000 episodes
Summary of resultsSummary of results
High heterogeneity in treatment offer
Apparent PTC’s preference towards abstinence oriented therapies (70% of patients at their first visit)
Methadone Maintenance offered on avearage at lower doses than those known to be effective (40 mg/day)
a range of specialist drug treatments are protective, substantially reducing the risk of drug related overdose during treatment
the risk of death is substantially higher in the month after treatment discharge or drop out;
leading to an excess of 6 deaths per 10,000 treatment episodes lasting less than one month
What to change if designing a new Vedette studyWhat to change if designing a new Vedette study
Necessisity to simplify information collected on treatment
Is there a better way to collect information on treatment?
18 months of follow-up. Is it a too short period? 100 deaths after 18 months, 189 after 30 months.
Do we have to plan longer studies to evaluate treatments correctly?
Tretaments already ongoing at the start of the study are difficult to be analyzed. Who to enroll? How many?
Strenght points of the Vedette studyStrenght points of the Vedette study
Valuable information about effectiveness of treatments for drug-dependance on more than one outcome
An insight of treatment demand and offer
Mortality follow-up. Easy to be updated
It provides the unique possibility of studying the occurance of outcomes
in the “real world” where:Patients are not randomizedTreatments are not optimal
Resources are limited
Results from A STYSTEMATIC REVIEW OF the OBSERVATIONAL STUDIES ON TREATMENT OF OPIOID DEPENDENCE
Results from A STYSTEMATIC REVIEW OF the OBSERVATIONAL STUDIES ON TREATMENT OF OPIOID DEPENDENCE
Review: Observational studies on treatment for opioid dependence and mortality Outcome: Comparison:
any cause mortality in methadone maintenance vs out of methadone maintenance
Study in MMT out MMT RR (random) Weight or sub-category n/N n/N 95% CI %
Davoli, Italy 1998-2001
27/5751 24/998 15.04 0.20 [0.11, 0.34] Caplehorn, Australia 1970-1991 11/1975 36/2279 11.17 0.35 [0.18, 0.69] Fugelstad, Sweden 1986-1993 7/177 33/330 8.60 0.40 [0.18, 0.88] Appel, USA 1966-1976
93/6118 83/2358 28.72 0.43 [0.32, 0.58] Brugal, Spain 1992-1999
119/5400 887/17649 36.46 0.44 [0.36, 0.53]
Total (95% CI) 19421 23614 100.00 0.37 [0.29, 0.48] Total events: 257 (in MMT), 1063 (out MMT) Test for heterogeneity: Chi² = 7.98, df = 4 (P = 0.09), I² = 49.9% Test for overall effect: Z = 7.44 (P < 0.00001)
0.001 0.01 0.1 1 10 100 1000 Favours treatment Favours control
Outcome:
Overdose mortality Comparison in methadone maintenance vs out of methadone maintenance
Study in MMT out MMT RR (random) Weight or sub-category n/N n/N 95% CI %
Davoli, Italy 1998-2001
7/5751 9/998 19.78 0.13 [0.05, 0.36] Appel, USA1966-1976 2/6118 36/2358 17.62 0.02 [0.01, 0.09] Brugal, Spain1992-1999
11/5400 338/17649 21.30 0.11 [0.06, 0.19] Van Ameijdem, The Netherlands 1989-1995 8/1500 7/466 19.67 0.36 [0.13, 0.97] Buster, The Netherlands. 1986-1998 42/18747 26/10983 21.63 0.95 [0.58, 1.54]
Total (95% CI) Total events: 70 (in MMT), 416 (out MMT) Test for heterogeneity: Chi² = 53.93, df = 4 (P < 0.00001), I² = 92.6% Test for overall effect: Z = 2.66 (P = 0.008)
0.001 0.01 0.1 1 10 100 1000 Favours treatment Favours control
Results from A STYSTEMATIC REVIEW OF the OBSERVATIONAL STUDIES ON TREATMENT OF OPIOID DEPENDENCE
Results from A STYSTEMATIC REVIEW OF the OBSERVATIONAL STUDIES ON TREATMENT OF OPIOID DEPENDENCE
What do you need to implement a study similar to Vedette?What do you need to implement a study similar to Vedette?
1 Ministry1 Ministry
2 coordination centres2 coordination centres
10 researchers10 researchers
13 regions13 regions
119 treatment services119 treatment services
+ di 1000 health operators+ di 1000 health operators
+ di 15000 clients+ di 15000 clients
and and
A strong collaboration among the A strong collaboration among the coordination centres and the servicescoordination centres and the services
It contributed to spread the aweraness of the importance of evidence based practice,
and of quantitative evaluation of treatments
CONCLUSIONCONCLUSION
The Vedette study is still ongoing:
Imputing missing treatment to use all the deaths registered at the last vital status ascertainmentContinuing the analysis of the effect of short-period treatmentsUpdating the follow-up of mortalityDesigning a nested case-control study to better understand the determinants of overdose mortalityOngoing follow-up on treatments on a sub-cohort (one region). . . . . . . . . . . . . . . . . . . . . . .
CONCLUSIONCONCLUSION
Do you think it would be
valuable
feasible
to replicate the Vedette study in other European countries?